Our studies are directed towards understanding genetic and developmental regulation of neurotransmitter metabolism. Catecholamine metabolism is examined in cultured cells by chromatographic analysis of radioisotopically labelled metabolites and by enzymatic assays for monoamine oxidase (EC 1.4.3.4) and catechol-o-methyltransferase (EC 2.1.1.6). We are studying the expression of the A and B forms of monoamine oxidase in rat hepatoma cells, mouse neuroblastoma cells and human skin fibroblasts. Monoamine oxidase activity is lowered in cells lacking hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) activity and we are exploring this phenomenon, which may correlate with the neurologic dysfunction in the Lesch-Nyhan syndrome. We are also characterizing properties of neurotransmitter metabolism expressed on human skin fibroblasts, including the above degradative enzymes, as well as membrane receptors for norepinephrine and acetylcholine. We will use fibroblasts from patients to study alterations in these properties associated with certain inherited diseases of the nervous system.